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Anti-microbial activities of saliva

Anti-microbial activities of saliva. Time course of sIgA appearance. Gestation. Birth. 8w. 11w. 19w. 26w. 2-4w. 1m. 3m. 6m. 2y. ?. SC Bronchial Epithel- ium. SC Salivary Gland. Saliva: Adult SC No IgA. Salivary Antibody to Initial Oral and Gut Flora. Tooth Eruption.

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Anti-microbial activities of saliva

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  1. Anti-microbial activities of saliva

  2. Time course of sIgA appearance Gestation Birth 8w 11w 19w 26w 2-4w 1m 3m 6m 2y ? SC Bronchial Epithel- ium SC Salivary Gland Saliva: Adult SC No IgA Salivary Antibody to Initial Oral and Gut Flora Tooth Eruption Adult Concen- trations Peyer’s Patches IgA Cells Saliva sIgA Early IgA Peak Many Salivary IgA Concentrations in Adult Range Adapted from Taubman & Smith, 1993

  3. Non-immunoglobulin anti-microbial agents in whole saliva

  4. Lactoferrin • Binds ferric iron (Fe3+) and unavailable for microbes • Nutritional immunity • Some microorganisms (e.g., E. coli) have adapted to this mechanism by producing enterochelins. • bind iron more effectively than lactoferrin • iron-rich enterochelins are then reabsorbed by bacteria • Lactoferrin, with or without iron, can be degraded by some bacterial proteases. • In unbound state, a direct bactericidal effect

  5. Lysozyme • Present in numerous organs and most body fluids • Oral LZ is derived from at least four sources • major and minor salivary glands, phagocytic cells and gingival crevicular fluid (GCF) • Biological function • Classic concept of anti-microbial activity of LZ is based on its muramidase activity (hydrolysis of (1-4) bond between N-acetylmuramic acid and N-acetylglucosamine in the peptidoglycan layer. • Gram negative bacteria generally more resistant than gram positive because of outer LPS layer

  6. Other anti-microbial activities of LZ • Muramidase activity (lysis of peptidoglycan layer) • Cationic-dependent activation of bacterial autolysins • strongly cationic protein (pI 10.5-11) • disrupts membranes • Aggregation of bacteria • Inhibition of bacterial adhesion to tooth surfaces • Inhibition of glucose uptake and acid production • De-chaining of streptococci

  7. Salivary peroxidase systems • Sialoperoxidase (SP, salivary peroxidase) • Produced in acinar cells of parotid glands • Also present in submandibular saliva • Readily adsorbed to various surfaces of mouth • enamel, salivary sediment, bacteria, dental plaque • Myeloperoxidase (MP) • From leukocytes entering via gingival crevice • 15-20% of total peroxidase in whole saliva

  8. Components of the peroxidase anti-microbial system • Peroxidase enzymes (SP or MP) • Hydrogen peroxide (H2O2) • oral bacteria (facultative aerobes/catalase negative) produce large amounts of peroxide • S. sanguis, S. mitis, S. mutans • Thiocyanate ion (SCN-) which is converted to hypothiocyanite ion (OSCN-) by peroxidase • salivary concentration is related to diet and smoking habits

  9. SP and/or MP H2O2 + SCN- OSCN- +H2O Thiocyanate reactions • The pK for HOSCN/OSCN- is 5.3 • More acid favors HOSCN • Due to uncharged nature, HOSCN penetrates bacterial cell envelope better Acid/Base Equilib. HOSCN OSCN- + H+ Hypothiocyanite ion Hypothiocianous acid

  10. HOSCN/OSCN--mediated cell damage • can oxidize sulfhydryl groups of enzymes • block glucose uptake • inhibit amino acid transport • damage inner membrane, leading to leakage of cell • disrupt electrochemical gradients

  11. Unstimulated bacteria Inhibited bacteria Active bacteria Regulation of oral microorganisms by SP/MP Food Ingestion Recovery carbohydrates Stimulation thiols spontaneous O2 Autoinhibition H+ OSCN-/HOSCN SCN- + H2O2 Metabolism Inhibition +SP Salivary Glands

  12. Histatins • A group of small histidine-rich proteins • Potent inhibitors of Candida albicans growth • Histatin 1, which is phosphorylated modulates precipitation of calcium phosphates

  13. Amylases • Well-known function as a digestive enzyme • Calcium metalloenzyme, which hydrolyses the (1-4) bonds of starches, such as amylose and amylopectin. • Anti-microbial activity • potent inhibitor and specific inhibitor of N. gonorrheoeae and Legionella pneumonophilain vitro. • modulates adhesion of certain oral species to teeth and other body surfaces

  14. Cystatins • Are inhibitors of cysteine-proteases • Are ubiquitous in many body fluids • Considered to be protective against unwanted proteolysis • bacterial proteases • lysed leukocytes • May play inhibit proteases in periodontal tissues • Also have an effect on calcium phosphate precipitation

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